Nitrogen → (E)-Ethyl 3-(5-(8-morpholino-2-(2-(quinolin-2-yl)vinyl)imidazo[1,2-b]pyridazin-3-yl)pyridin-2-yl)propanoate

HRID 718663Notes

Reaction equation

HRID 718663 reaction equation
[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1/[CH:11]=[CH:12]/[C:13]1[N:14]=[C:15]2[C:20]([N:21]3[CH2:26][CH2:25][O:24][CH2:23][CH2:22]3)=[CH:19][CH:18]=[N:17][N:16]2[CH:27]=1.Br[C:29]1[CH:30]=[CH:31][C:32]([CH2:35][CH2:36][C:37]([O:39][CH2:40][CH3:41])=[O:38])=[N:33][CH:34]=1.N#N.CC([O-])=O.[K+].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2].O>[O:24]1[CH2:23][CH2:22][N:21]([C:20]2[C:15]3[N:16]([C:27]([C:29]4[CH:30]=[CH:31][C:32]([CH2:35][CH2:36][C:37]([O:39][CH2:40][CH3:41])=[O:38])=[N:33][CH:34]=4)=[C:13](/[CH:12]=[CH:11]/[C:2]4[CH:3]=[CH:4][C:5]5[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=5)[N:1]=4)[N:14]=3)[N:17]=[CH:18][CH:19]=2)[CH2:26][CH2:25]1

Participants

9

Reactant 5

HCID 947NitrogenHCID 11776TriphenylphosphineHCID 517044Potassium AcetateHCID 117728317Ethyl 3-(5-bromopyridin-2-yl)propanoateHCID 117728366(E)-4-(2-(2-(Quinolin-2-yl)vinyl)imidazo[1,2-b]pyridazin-8-yl)morpholine

Product 1

HCID 117732511(E)-Ethyl 3-(5-(8-morpholino-2-(2-(quinolin-2-yl)vinyl)imidazo[1,2-b]pyridazin-3-yl)pyridin-2-yl)propanoate

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
105 °C

Procedure

A solution of compound 57c (0.90 g, 2.5 mmol) and compound 57b (0.96 g, 3.7 mmol) in DMF (5 mL) was purged with N2. Pd(OAc)2 (67 mg, 0.30 mmol) was added, followed by KOAc (1.1 g, 11 mmol) and PPh3 (73 mg, 0.28 mmol). The resulting mixture was stirred at 105° C. for 1.5 h, and allowed to cool to rt. water (100 mL) was added. The resulting mixture was extracted with DCM (3×50 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure. The residue obtained was purified by flash column chromatography on silica gel (EtOAc/petroleum ether (1:2-2:1 v/v)) to obtain compound 57d as a yellow solid. Mass Spectrum (LCMS, ESI pos.): Calcd. for C31H30N6O3: 535.2 (M+H). Found: 535.2.

Workup

  1. temperatureto cool to rt
  2. extractionThe resulting mixture was extracted with DCM (3×50 mL)
  3. dry with materialThe combined organic layers were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue obtained
  7. customwas purified by flash column chromatography on silica gel (EtOAc/petroleum ether (1:2-2:1 v/v))

Sources & evidence

ORD record
ord-b56930a33dc34a949227f060a231fc70
Source dataset
uspto-grants-2015_11
Patent number
US09193736B2

Reaction notes

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